title: Development, optimization and in vitro evaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery.
abstract: The present research work was aimed at development and optimization of alginate mucoadhesive microspheres of carvedilol for nasal delivery to avoid first pass metabolism and to improve the therapeutic efficacy in the treatment of hypertension and angina pectoris. The microspheres were prepared by a water-in-oil (w/o) emulsification technique. A 2(3) factorial design was employed with drug : polymer ratio, calcium chloride concentration and cross-linking time as independent variables while particle size of the microspheres and in vitro mucoadhesion were the dependent variables. Regression analysis was performed to identify the best formulation conditions. Particle size was analysed by dynamic laser light diffraction technique and found to be in the range of 26.36-54.32 microm, which is favourable for intranasal absorption. The shape and surface characteristics were determined by scanning electron microscopy (SEM) which depicted the spherical nature and nearly smooth surfaces of the microspheres. The percentage encapsulation efficiency was found to be in the range between 36.62-56.18. In vitro mucoadhesion was performed by adhesion number using sheep nasal mucosa and was observed in a range from 69.25-85.28. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of carvedilol in the microspheres. In vitro release studies in pH 6.2 phosphate buffer indicated non-Fickian or anomalous type of transport for the release of carvedilol from the microspheres.
authors.affiliation: New Drug Delivery Research Laboratory, TIFAC Center of Relevance and Excellence in NDDS, Pharmacy Department, The M. S. University of Baroda, Fatehgunj, Vadodara, Gujarat, India.
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Patil
authors.forename: Krutika K
authors.initials: KK
authors.lastname: Sawant
mesh_terms: D000268:Adhesiveness; D000281:Administration, Intranasal; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism; D002122:Calcium Chloride / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism*; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical; D003432:Cross-Linking Reagents / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009297:Nasal Mucosa / Q000378:metabolism*; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011412:Propanolamines / Q000737:chemistry / Q000378:metabolism*; D012756:Sheep; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000464:Alginates; D000959:Antihypertensive Agents; D002227:Carbazoles; D003432:Cross-Linking Reagents; D004655:Emulsions; D006603:Hexuronic Acids; D009821:Oils; D011412:Propanolamines; D014867:Water; D000077261:Carvedilol; D020723:Glucuronic Acid; D002122:Calcium Chloride